{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:20:46Z","timestamp":1788268846884,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ischemic stroke triggers neuroinflammation and oxidative stress, leading to neuronal damage. Kojic acid (KA) has exhibited neuroprotective properties in other neurological pathologies but suffers from poor bioavailability. This study investigated whether KA encapsulated in nanostructured lipid carriers (KA\u2010NLC) exerts protective effects against cerebral ischemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eighty adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) or control procedures and allocated into 10 experimental groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098 per group): intact, sham, MCAO, vehicle, three free\u2010KA solution groups (10, 20, and 40\u2009mg\/kg), and three KA\u2010NLC groups (1, 2, and 4\u2009mg\/kg). Functional outcomes were assessed using neurological scoring and Rota\u2010Rod, Morris water maze, and shuttle box tests. Brain water content, hippocampal histology, and cerebrospinal fluid cytokine levels (interleukin\u201010 [IL\u201010], tumor necrosis factor\u2010\u03b1 [TNF\u2010\u03b1]) were also evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment with low and medium doses of KA\u2010NLC and medium and high doses of free KA significantly reduced brain edema and improved neurological scores, motor coordination, and memory performance compared to the MCAO group. These functional improvements were associated with a significant increase in anti\u2010inflammatory IL\u201010 and a modulation of TNF\u2010\u03b1. Histological examination confirmed neuroprotection, with KA\u2010NLC preserving hippocampal CA1 neural integrity. The high dose of KA\u2010NLC and the low dose of free KA however were ineffective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Nanoformulated KA confers significant neuroprotection against ischemic stroke by reducing edema, modulating inflammation, and preserving neuronal integrity, presenting a promising therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70285","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:49:28Z","timestamp":1788266968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotection after transient middle cerebral artery occlusion in male rats using kojic acid nanostructured lipid carriers: A behavioral, biochemical, and histological study on hippocampal\n                    <scp>CA1<\/scp>\n                    region"],"prefix":"10.1002","author":[{"given":"Mobina","family":"Gheibi","sequence":"first","affiliation":[{"name":"Student Research Committee, School of Allied Medical Sciences Mazandaran University of Medical Sciences  Sari Iran"},{"name":"Non\u2010Communicable Diseases Institute, Mazandaran University of Medical Sciences  Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erfan","family":"Ghadirzadeh","sequence":"additional","affiliation":[{"name":"Non\u2010Communicable Diseases Institute, Mazandaran University of Medical Sciences  Sari Iran"},{"name":"Student Research Committee, School of Medicine Mazandaran University of Medical Sciences  Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javid","family":"Tebyani","sequence":"additional","affiliation":[{"name":"Student Research Committee, School of Medicine Mazandaran University of Medical Sciences  Sari 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University of Medical Sciences  Sari Iran"},{"name":"Psychiatry and Behavioral Sciences Research Center Addiction Institute, Mazandaran University of Medical Sciences  Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narges","family":"Karimi","sequence":"additional","affiliation":[{"name":"Department of Neurology Mazandaran University of Medical Sciences  Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melika","family":"Pourhossein","sequence":"additional","affiliation":[{"name":"Student Research Committee, School of Pharmacy Mazandaran University of Medical Sciences  Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Shadi","sequence":"additional","affiliation":[{"name":"Student Research Committee, School of Medicine Mazandaran University of Medical Sciences  Sari 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